This research program is directed at elucidating the role of hormone receptors in the mechanism of action of glucocorticoids. The goal of the poposal, in the forthcoming grant period, is to study the plasa carrier, various tissue binders and the cytoplasmic receptors for glucocorticoids as they interact in the process of transferring the hormone from plasma to cell nucleus. The long range objectives are to gain insight into various aspects of hormone action so that this information can be applied to improve our understanding of normal steroid physiology, adrenal pathophysiology and the pharmacology of glucocorticoids. The systems to be employed are in vivo, in vitro and cell culture studies using the rat as the experimental animal. The primary target organs of interest will be kidney and thymusg land. Glucocorticoids bind to a heterogeneous group of binding components including the plasma carrier corticosteroid binding globulin (CBG), the cytoplasmic receptor and other tissue binders localized to the cell membrane or other intracellular sites. The focus of this project will be to understand how these various glucocorticoid binding components contribute to and modulate the ultimate physiological expression of the hormone. The first section of the research plan includes projects which define the properties of the carrier/binder receptor binding components including: (a) recognition of the heterogeneity of the multiple binding components, (b) assessment of the regulation of these binding components, and (c) evaluation of how changes in these binding components modulate glucocorticoid functional expression. The second section applies this information in specific situations including: (a) stress and the use of glucocorticoids therapeutically, (b) regulation of CBG as it affects glucocorticoid efficacy and (c) the adrenal gland as a glucocorticoid target organ. A multiphasic experimental design is planned subjecting several different but related aspects of steroid action to investigation. It is hoped that the interrelationships developed by this approach will significantly add to our understanding of glucocorticoid action.